1. Field of the Invention
The present invention relates to methods and compositions for modulating immune response in a mammal.
2. Description of the Background
An immune response to an antigenic agent, be it a foreign antigen or an auto-antigen, is generally characterized by the production of antibodies by B lymphocytes and/or by destruction by T lymphocytes and/or natural killer (NK) cells of any cells displaying those antigens. Defects in B and/or T lymphoid cells, however, may result in the development of immunodeficiency diseases and/or the impairment of immune response function. The immune deficiency or defect may be congenital, caused by a mutation in a gene, or it may be acquired, for example, through a viral infection or as a result of the aging process. The thus produced defect may or may not be fatal, depending on the stage of stem cell or lymphocyte differentiation at which it occurs.
X-linked or Bruton's-type agammaglobulinaemia, for example, is an immunodeficiency disease known to result from a defect in B-cell differentiation. Although the differentiation of T lymphocytes proceeds near normally, in general, few mature B lymphocytes develop. As a result, the levels of all major classes of immunoglobulins are drastically reduced in this disease, and this defect makes most patients vulnerable to bacterial infections. X-linked agammaglobulinaemia may be treated by periodic intramuscular inoculations of immune globulin, that provide a minimal level of antibody protection against at least some infectious diseases. Repeated intramuscular injections, however, are costly, painful, often lead to local scarring, and may produce severe anaphylactic-like reactions. Repeated intravenous plasma infusion is an alternative therapy which is occasionally used. Each infusion, however, takes several hours, and requires plasma from a single donor, who must be free of microbial contamination, e.g., hepatitis virus-free. Immune globulin formulated for intravenous administration is also available, but extremely costly.
In Wiskott-Aldrich syndrome, immunological defects occur in both T and B lymphocytes. The number of T cells in Wiskott-Aldrich syndrome patients decreases progressively, while the number of B cells expands, IgM levels are lower, and total IgG concentrations are normal. Afflicted patients do not make antibodies to polysaccharide antigens, and respond poorly to protein antigens. This disease may only be treated at the present time by bone marrow transplantation, but only if a histocompatible donor is available.
It is, therefore, highly desirable to identify relatively inexpensive, non-toxic, easily administered agents which are suitable for enhancing the immune response of mammals afflicted with an immunodeficiency disease(s), and/or for accelerating and enhancing the immune response of normal and elderly mammals when clinically indicated. It is also desirable in some instances to inhibit or suppress an immune response, such as in transplants.